Edirol (eldecalcitol) / Roche, Taisho - LARVOL DELTA

Risperidone induces osteoporosis and neuropsychiatric treatment resistance via SMPD1-lysosome-mediated ferroptosis: dual rescue by active vitamin D analog ED-71. (PubMed, J Adv Res) - "This study identifies SMPD1 activation as a therapeutic target to counteract RIS-induced ferroptosis in bone and hippocampus. The dual-action mechanism of ED-71 provides a novel strategy for SZ intervention, simultaneously addressing psychiatric symptoms and osteoporotic complications."

Journal • CNS Disorders • Osteoporosis • Psychiatry • Rheumatology • Schizophrenia

Distribution effect of SOST on alveolar bone micro-bone formation in rats induced by Eldecalcitol. (PubMed, Eur J Med Res) - "This study reveals the distribution of TRAP-positive osteoclasts and sclerostin-positive osteocytes in the alveolar septal area and their correlation with bone metabolism-related factors. Eldecalcitol treatment effectively inhibits osteoclast activity, reduces bone resorption, and significantly mitigates the reduction of sclerostin expression in osteocytes induced by ovariectomy. These findings suggest that Eldecalcitol may regulate alveolar bone metabolism partially by modulating sclerostin expression, making it a promising therapeutic strategy for osteoporosis."

Journal • Preclinical • Osteoporosis • Rheumatology • SOST

Eldecalcitol Ameliorates Type 2 Diabetic Osteoporosis by Attenuating Endothelial Ferroptosis via the SOCE/O-GlcNAcylation Axis. (PubMed, Free Radic Biol Med) - "When exploring the potential mechanism of action, we observed that ED71 suppressed ferroptosis by rescuing store-operated calcium entry (SOCE) mediated calcium signaling and subsequently normalizing aberrant O-GlcNAcylation, and the introduction of the SOCE inhibitor 2-aminoethyl diphenylborinate (2APB) and the OGlcNAcylation inhibitor OSMI-1 counteracted the beneficial effects of ED71 in HGHF-treated endothelial cells. In conclusion, these data suggest that ferroptosis of endothelial cells is associated with T2DOP, and ED71 can regulate ferroptosis of endothelial cells through the SOCE/OGlcNActlation aixs, thereby targeting and modulating bone homeostasis."

Journal • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • Type 2 Diabetes Mellitus

Study on the Intervention Effect of Denosumab on High-Risk Patients With Osteoporotic Fractures in Type 2 Diabetes (clinicaltrials.gov) - P=N/A | N=310 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital

New trial • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • Type 2 Diabetes Mellitus

Efficacy of 12-month romosozumab monotherapy or combination with eldecalcitol in patients with osteoporosis with and without chronic kidney disease: A real-world retrospective study. (PubMed, Biomed Rep) - "ROMO demonstrated efficacy in the treatment of osteoporosis, irrespective of renal function. ROMO + ELD treatment may be beneficial for patients with CKD."

Journal • Monotherapy • Real-world evidence • Retrospective data • Chronic Kidney Disease • Nephrology • Osteoporosis • Renal Disease • Rheumatology

Recent Advancements Towards the Use of Vitamin D Isoforms and the Development of Their Synthetic Analogues as New Therapeutics. (PubMed, Biomedicines) - "Several analogues, such as alfacalcidol, paricalcitol, and falecalcitriol, are used for managing CKD-related bone disorders, while eldecalcitol is effective for osteoporosis, and calcipotriol against psoriasis. Advanced analytical techniques such as LC/ESI-MS/MS facilitate precise detection of vitamin D metabolites, further improving pharmacokinetic profiling. Future research may enable the clinical approval of novel vitamin D-based therapeutics with minimal disruption to calcium-phosphorus balance."

Journal • Review • Asthma • Dermatology • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Oncology • Osteoporosis • Psoriasis • Pulmonary Disease • Respiratory Diseases • Rheumatology • EGFR • KRAS

Therapeutics for Sarcopenia and Functional Disabilities in Older Adults: A Review of Phase 4 Clinical Trials. (PubMed, Drug Des Devel Ther) - "Several therapeutic agents, including whey protein powder, eldecalcitol, testosterone enanthate, and Denosumab, have been tested in Phase 4 trials for their ability to enhance muscle mass and function in older adults with sarcopenia. Allopurinol and Pioglitazone were also studied for their potential to improve muscle metabolism, while Medrol (Methylprednisolone) and Levothyroxine offered supportive effects in inflammatory and metabolic disorders that exacerbate muscle loss...Phase 4 clinical trials provide valuable insights into the long-term safety and effectiveness of these treatments. Continued research and refinement of these therapies are essential to fully address the disabling effects of sarcopenia and promote healthy aging."

Journal • P4 data • Review • Metabolic Disorders • Sarcopenia

Anti-sarcopenic effects of active vitamin D through modulation of anabolic and catabolic signaling pathways in human skeletal muscle: A randomized controlled trial. (PubMed, Metabolism) - "This study suggested that the active form of vitamin D regulates the protein synthesis and degradation pathways in human skeletal muscle and may help prevent sarcopenia. This study was registered at UMIN clinical trials registry, UMIN 000005394."

Journal • Diabetes • Metabolic Disorders • Sarcopenia

ED-71 ameliorates OVX-induced osteoporosis by regulating calcium homeostasis and SIRT1-mediated mitochondrial function, alleviating osteoblast senescence and suppressing osteoclastogenesis. (PubMed, Cell Signal) - "This alleviates mitochondrial dysfunction and promotes adenosine triphosphate (ATP). The combined effects of these two factors synergistically contribute to the improvement in osteoblast senescence."

Journal • Metabolic Disorders • Osteoporosis • Rheumatology • PERK • SIRT1 • TNFRSF11B

A Case of Hypercalcemia with the Oral Administration of Active Vitamin D3 and Chinese Herbal Medicine. (PubMed, Intern Med) - "The patient had been treated at several medical institutions, with one institution administering eldecalcitol and another institution administering Keishikaryukotsuboreito, Borei powder, and Goreisan. The patient presented with drug-induced hypercalcemia due to an unexpected synergistic effect. Confirmation of prescriptions for patients with multiple medical visits and recognition of the components and side effects of Chinese herbal medicines is thus considered to be extremely important."

Journal • Endocrine Disorders • Metabolic Disorders

Changes in the Serum Calcium Level and Renal Function after Switching from Alfacalcidol to Eldecalcitol (PubMed, Yakugaku Zasshi) - "The estimated glomerular filtration rate didn't change significantly in any group during hospitalization. These results suggest that serum Ca levels should be measured by Week 2 when ELD is newly started or changed."

Journal • Acute Kidney Injury • Endocrine Disorders • Metabolic Disorders • Renal Disease

Determination of eldecalcitol in human plasma by SIL-IS UPLC-APCI-MS/MS method for pharmacokinetics study. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "This method was validated regarding selectivity, LLOQ, linearity, accuracy and precision, recovery, matrix effects, dilution reliability, stability, carryover test, and incurred sample reanalysis (ISR). This methodology had been successfully employed to assess the pharmacokinetics (PK) profile of eldecalcitol in a clinical investigation."

Journal • PK/PD data • Osteoporosis • Rheumatology

CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels. (PubMed, J Zhejiang Univ Sci B) - "Moreover, treatment of cells with the GPX1 inhibitor eldecalcitol (ED-71) revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group. In conclusion, CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway. Thus, targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CXCL16 • GPX1

Eldecalcitol Add-On to Risedronate Reduces Bone Loss from Aromatase Inhibitors in Postmenopausal Breast Cancer Patients. (PubMed, J Clin Endocrinol Metab) - "Eldecalcitol add-on therapy increased LS-BMD in osteopenic to osteoporotic postmenopausal women treated with an AI and risedronate."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Osteoporosis • Rheumatology • Solid Tumor

Eldecalcitol alleviates diabetic periodontitis by regulating macrophage efferocytosis and polarization via SOCE machinery. (PubMed, Int Immunopharmacol) - "In conclusion, diabetes impairs macrophage efferocytosis and M2 polarization in periodontitis rats, resulting in the delayed resolution of inflammation. ED-71 could attenuate alveolar bone loss by mitigating macrophage via SOCE machinery in DPD."

Journal • Dental Disorders • Diabetes • Inflammation • Metabolic Disorders • Osteoporosis • Periodontitis • Type 2 Diabetes Mellitus • TRAP

Pharmacologic or genetic interference with atrogene signaling protects from glucocorticoid-induced musculoskeletal and cardiac disease. (PubMed, JCI Insight) - "Activation of Vitamin D receptor (VDR) signaling with the VDR ligands 1,25D3 (calcitriol, 1,25-dihydroxyvitamin D3) or ED (eldecalcitol, 2β-(3-hydroxypropyloxy)-1,25-dihydroxyvitamin D3) prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of three tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ∆RING mice afforded temporary or sustained protection from GC excess in bone, or skeletal and heart muscle, respectively. We conclude that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the three tissues."

Journal • Cardiovascular • Heart Failure • Musculoskeletal Diseases • Orthopedics • Targeted Protein Degradation

ED-71 promotes osseointegration of titanium implants in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner. (PubMed, J Oral Biosci) - "ED-71 promoted implant osseointegration in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner."

Journal • Preclinical • Inflammation • Orthopedics • Osteoporosis • Rheumatology • SIRT1

Eldecalcitol ameliorates diabetic osteoporosis and glucolipid metabolic disorder by promoting Treg cell differentiation through SOCE. (PubMed, Cell Mol Life Sci) - "The SOCE inhibitor, 2-APB, partially attenuated the positive effects of ED-71 observed in the above results. Overall, ED-71 regulates SOCE-mediated Treg cell differentiation, accomplishing the dual purpose of simultaneously ameliorating diabetic osteoporosis and glucolipid metabolic disorders, showcasing its potential in osteoimmunity therapy and interventions for diseases involving SOCE."

Journal • Diabetes • Dyslipidemia • Metabolic Disorders • Obesity • Osteoporosis • Rheumatology • Type 2 Diabetes Mellitus • CD4 • IL2RA • STIM1

A pharmacovigilance study on clinical factors of active vitamin D3 analog-related acute kidney injury using the Japanese Adverse Drug Event Report Database. (PubMed, Sci Rep) - "There was a significant association between AKI and active vitamin D3 analogs (ROR [95% confidence interval {CI}], eldecalcitol: 16.75 [14.23-19.72], P < 0.001; alfacalcidol: 5.29 [4.07-6.87], P < 0.001; calcitriol: 4.46 [1.88-10.59], P < 0.001)...Our results suggest that active vitamin D3 analogs are associated with AKI development. Physicians prescribing these medications to patients with risk factors should consider the possibility of AKI, especially during the first 6 months."

Adverse events • Journal • Acute Kidney Injury • Cardiovascular • Hypertension • Nephrology • Osteoporosis • Renal Disease • Rheumatology

ED-71 Ameliorates Bone Loss in Type 2 Diabetes Mellitus by Enhancing Osteogenesis Through Upregulation of the Circadian Rhythm Coregulator BMAL1. (PubMed, Drug Des Devel Ther) - "The inhibition of SIRT1 with EX527 partially attenuated ED-71's effects, whereas the GSK3β inhibitor LiCl further enhanced ED-71's positive effects on BMAL1 expression. ED-71 ameliorates bone loss in T2DM by upregulating the circadian rhythm coregulator BMAL1 and promoting osteogenesis through inhibition of oxidative stress. The SIRT1/GSK3β signaling pathway is involved in the regulation of BMAL1."

Journal • Diabetes • Metabolic Disorders • Osteoporosis • Type 2 Diabetes Mellitus • ARNTL • BMAL1

The potential effect of romosozumab on perioperative management for instrumentation surgery. (PubMed, JOR Spine) - "This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management."

Journal • Surgery • Orthopedics • Osteoporosis • Rheumatology

Clinical Intervention of Idecalcitol Combined With Whey Protein Powder and Exercise for Sarcopenia (clinicaltrials.gov) - P4 | N=450 | Recruiting | Sponsor: Zhejiang Provincial People's Hospital

New P4 trial • Sarcopenia

Eldecalcitol Inhibits Bone Turnover and Increases Bone Mass and Strength by Promoting RANK Expression in BMSCs (ASBMR 2024) - No abstract available

A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis. (PubMed, Drug Des Devel Ther) - "To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals...Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs."

Journal • Osteoporosis • Rheumatology

Bone management for breast cancer patients (JBCS 2024) - "Concomitant medications with zoledronic acid were none in 42 cases, calcium preparations in 2 cases, alphacalcidol in 4 cases, and eldecalcitol in 26 cases. The median age of the 74 cases treated with zoledronic acid was 70.0 years (55-86 years). Histological diagnosis was DCIS in 4 cases and invasive cancer in 70 cases. Subtypes were luminal type in 64 cases and luminal HER2 type in 6 cases."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Musculoskeletal Diseases • Nephrology • Oncology • Osteoporosis • Renal Disease • Rheumatology • Solid Tumor • HER-2